Method and apparatus for sensing a stimulating gastrointestinal tract on-demand

ABSTRACT

Method and apparatus for providing on-demand stimulation of the gastrointestinal tract. The apparatus features an implantable pulse generator which may be coupled to the gastric system through one or more medical electrical leads. In the preferred embodiment the leads couple to the circular layer of the stomach. The pulse generator preferably features sensor for sensing abnormalities in gastric electrical activity. The pulse generator further features means for recognizing the type of gastric abnormality sensed. That is means for detecting whether gastric arrhythmia, bradygastria, dysrhythmia, tachygastria or retrograde propagation or uncoupling are present. If any of these gastric rhythm abnormalities are detected, then the pulse generator features means for emitting stimulation pulse trains to the gastric system to treat the detected gastric rhythm abnormalities. The stimulation pulse trains may take many forms and may be emitted for various periods of time.

FIELD OF THE INVENTION

The invention relates to the field of smooth muscle disorders. Inparticular, the invention relates to treatment of gastrointestinaldisorders using a method and apparatus for providing on-demandstimulation of the gastrointestinal tract.

BACKGROUND OF THE INVENTION

The gastrointestinal tract is responsible for an essential step in thedigestive process, the reception of nutrition in the human body.Nutrition is received by absorbing mucosa in the gastrointestinal tract,using a very complex mechanism. An important element of the digestiveprocess is intestinal peristalsis, the coordinated and self-regulatedmotor activity of the intestinal tract. Peristalsis is accomplishedthrough a coordinated combination of electrical, chemical, and hormonalmediation, possibly in addition to other unknown mechanisms.

It is known that many diseases and maladies can affect the motoractivity of the gastrointestinal tract, causing malfunction of thedigestive process. Such diseases include diabetes mellitus, scleroderma,intestinal pseudo-obstruction, ileus, and gastroparesis. Other maladiessuch as tachygastria or bradygastria can also hinder coordinatedmuscular motor activity of the bowel.

Gastroparesis, for example, is a chronic gastric motility disorder inwhich there is delayed gastric emptying of solids plus or minus liquids.Symptoms of gastroparesis may range from early satiety and nausea inmild cases to chronic vomiting, dehydration, and nutritional compromisein severe cases. Diagnosis of gastroparesis is based on demonstration ofdelayed gastric emptying of a radio-labeled solid meal in the absence ofmechanical obstruction. A number of gastrointestinal and systemicdisorders may impair gastric motility with resultant gastroparesis.Approximately one third of patients with gastroparesis have noidentifiable underlying cause (often called idiopathic gastroparesis).Management of gastroparesis involves four areas: (1) nutritionalsupport, (2) antiemetic drugs, (3) prokinetic drugs, and (4) surgicaltherapy (in a very small subset of patients.) Gastroparesis is often achronic, relapsing condition; 80% of patients require maintenanceantiemetic and prokinetic therapy and 20% require long-term nutritionalsupplementation. In the near future, the most promising advances in thetreatment of patients with gastroparesis will most likely come from thearea of combination pharmacological therapy. In the long term,developments in the area of gastrointestinal pacing and transplantationmay offer further treatment options in this difficult disorder.

The undesired effect of these conditions is a reduced ability orcomplete failure to efficiently propel gastrointestinal contents downthe digestive tract. This results in malassimilation of liquid or foodby the absorbing mucosa of the intestinal tract. If this condition isnot corrected, malnutrition or even starvation may occur. Whereas someof these disease states can be corrected by medication or by simplesurgery, in most cases treatment with drugs is not adequately effective,and surgery often has intolerable physiologic effects on the body.

It is known that motor activity can be recorded as electrical activityof the muscle. Traditionally, motor activity has been measured usingrecording electrodes placed directly on the muscle of thegastrointestinal tract, or on the skin external to the intestinal tract.For example, electrocardiograms measure the electrical activity of theheart in this manner.

Presently, however, there is no practically effective device or systemto stimulate, record, or intelligently alter the muscular contractionsof smooth muscle and the gastrointestinal tract in particular.Therefore, there is a need in the art for a system and method toproperly pace gastrointestinal motor activity for correcting ineffectiveor absent propulsive electrical muscular activity of thegastrointestinal tract.

The muscle in the gastrointestinal tract differs from muscle elsewherein two major ways. First, most of the muscle in the gastrointestinaltract is of the type called smooth muscle. There are several fundamentaldifferences between the way smooth muscle and skeletal muscle function.

First, smooth muscle lacks a discrete end-plate (a defined region ofinteraction between the nerve ending and muscle, as seen in skeletalmuscle); instead nerve fibers run from each axon parallel to the musclebundle and end somewhat arbitrarily at various points along its length.

Secondly, unlike skeletal muscle, smooth muscle cells are coupledelectrically within large bundles by means of connecting bridges. Anelectrical event at any region in the bundle is therefore conducted in adecremental fashion to other regions.

Thirdly, each muscle bundle receives input from multiple axons in theform of either excitatory or inhibitory signals. This is in contrast toskeletal muscle outside the gastrointestinal tract, where typically onlyone type of neurotransmitter is operative.

In addition, the gastrointestinal muscle is organized and regulated verydifferently than muscle elsewhere. Both skeletal and smooth muscle inthe gastrointestinal tract are under the control of the enteric nervoussystem which is an extremely complex network of nerves and muscles, thatresides within the gastrointestinal wall and orchestrates the entiredigestive process including motility, secretion and absorption. Theenteric nerves are also organized into interconnected networks calledplexuses. Of these, the myenteric plexus, situated between the circularand longitudinal muscle layers, is the main modulator ofgastrointestinal motility. It receives input from both the centralnervous system (via vagal and sympathetic pathways) as well as fromlocal reflex pathways. Its output consists of both inhibitory andexcitatory signals to the adjacent muscle.

The final neural pathway regulating muscle activity in thegastrointestinal tract is therefore represented by the neurons of themyenteric plexus. A useful, if somewhat simplistic concept is tovisualize net muscle tone in the gastrointestinal tract as thatresulting from the balance between the opposing effects of two neuronalsystems in the myenteric plexus: one causing the muscle to contract(mainly via acetylcholine) and the other causing it to relax. Both typesof neurons, however, are activated by acetylcholine within the myentericplexus. The role of acetylcholine in the regulation of gastrointestinalmuscle tone is therefore complex. Acetylcholine directly released byeffector nerves near the muscle causes contraction; however, within themyenteric plexus, it may result in inhibition or excitation. This is incontrast to skeletal muscle outside the gastrointestinal tract which isdirectly innervated by nerves emanating from the central nervous system.The interaction between nerve and muscle in skeletal muscle outside thegastrointestinal tract is far more simple: nerves release acetylcholinewhich causes the muscle to contract.

Finally, the myenteric plexus is probably the most important but not theonly determinant of muscle tone in the gastrointestinal tract. In fact,basal smooth muscle tone may be visualized as resulting from the sum ofmany different factors including intrinsic (myogenic) tone, andcirculating hormones, in addition to nerve activity.

It should be clear therefore, that the regulation of gastrointestinaltract muscle motility is far more complex than that of skeletal muscleoutside the gastrointestinal tract.

There is a need in the medical arts for methods and devices fortreatment of gastrointestinal disorders including achalasia, otherdisorders of the lower esophageal sphincter, sphincter of Oddidysfunction, irritable bowel syndrome, etc., which treatments will belong-lasting and devoid of significant rates of complication.

SUMMARY OF THE INVENTION

It is an object of the invention to provide methods for in vivotreatment of mammals with dysfunctional gastrointestinal muscle ordisorders of smooth muscles elsewhere in the body.

It is another object of the invention to provide a device for in vivotreatment of mammals with dysfunctional gastrointestinal muscle orsmooth muscles elsewhere in the body.

These and other objects are provided by one or more of the embodimentsdescribed below. The present invention is a method and apparatus forproviding on-demand stimulation of the gastrointestinal tract. Theapparatus features an implantable pulse generator which may be coupledto the gastric system through one or more medical electrical leads. Inthe preferred embodiment the leads couple to the circular layer of thestomach. The pulse generator preferably features sensor for sensingabnormalities in gastric electrical activity. The pulse generatorfurther features means for recognizing the type of gastric abnormalitysensed. That is means for detecting whether gastric arrhythmia,bradygastria, dysrhythmia, tachygastria or retrograde propagation oruncoupling are present. If any of these gastric rhythm abnormalities aredetected, then the pulse generator features means for emittingstimulation pulse trains to the gastric system to treat the detectedgastric rhythm abnormalities. The stimulation pulse trains may take manyforms and may be emitted for various periods of time.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-described and other aspects of the present invention may bebetter understood and appreciated with reference to a detaileddescription of a specific embodiment of the invention, when read inconjunction with the accompanying drawings, wherein:

FIG. 1 depicts the apparatus implanted within a patient.

FIG. 2 depicts a detailed view of the stomach muscle showing theelectrode of the lead implanted.

FIG. 3 depicts a plan view of a lead used with the apparatus.

FIG. 4 is a functional block diagram of the pulse generator.

FIG. 5 is a table listing the gastric arrhythmias or abnormalities whichmay be detected and treated using the present invention.

FIG. 6 which illustrates the detection interval ranges which may beemployed in a preferred embodiment of the present invention.

FIG. 7 is a functional block diagram illustrating the present invention.

FIG. 8 details the preferred stimulation pulse train emitted.

FIGS. 9-11 details the alternate stimulation pulse trains which may beemitted.

FIG. 12 depicts an exemplary EGG as detected by the present inventionand the emitted stimulation to treat a detected arrhythmia.

FIG. 13, this depicts a gastroarrhythmia which is detected due to thefact that the slew rate of the electrogastrogram is not normal.

FIG. 14 depicts a further gastric arrhythmia which is detected due tothe fact that is has a much lower amplitude.

FIG. 15 depicts an example of a gastroarrhythmia which is detected bythe present invention using cross-correlation.

FIG. 16 depicts an example of a gastro rhythm which is detected by thepresent invention using a series of frequency selective sensors.

FIG. 17 is a flow diagram of a device used to detect the rhythm shown inFIG. 16.

FIG. 18 shows a block diagram of an alternate embodiment of the presentinvention.

The FIGS. are not necessarily to scale.

DETAILED DESCRIPTION OF THE INVENTION

The following description is of the best mode presently contemplated forcarrying out the invention. This description is not to be taken in alimiting sense, but is made merely for the purpose of describing thegeneral principles of the invention. The scope of the invention shouldbe determined with reference to the claims. Moreover, although thedevice is particularly illustrated to treat the stomach, this is doneonly for purposes of illustration. The present invention may be used totreat any of the various organs and associated conditions of thegastrointestinal tract, including the large and small bowel, as well asthe esophagus.

FIG. 1 shows a system 1 implanted in a patient 2. As seen, the system 1comprises an implantable pulse generator 3 featuring two sets of leads4, 5 which are coupled to the stomach 10. The first set of leads 4provide stimulation to the stomach. The second set of leads 5 providesensing of the gastro electrical activity of the stomach 10 to the pulsegenerator 3. In the preferred embodiment, the pulse generator 3 isimplanted within the patient 2, and thus is hermetically enclosed, as iswell known in the art. The leads used for both the first set 4 and thesecond set 5 may be any acceptable lead. In the preferred embodiment,the preferred leads are Medtronic Model No. 4300 intramuscular lead. Ofcourse, other configurations of leads or lead systems may be used,including other leads designs as well as more or less sets of leads..

The first set of leads 4 are stimulation leads which conduct stimulationpulses from the pulse generator 3 to the stomach 10. First set of leads4 are preferably implanted at the junction of the corpus and antrum ofthe stomach 10 in essentially a line along the greater curvature runningfrom the fundus 11 to the terminal antrum 12. Of course, other locationsfor first set of leads 4 may be used, such as in the caudud corpus aswell as the orad or terminal antrum. The second set of leads 5 aresensing leads which conduct any gastroelectrical activities sensed inthe stomach 10 to the pulse generator 3. Preferably the second set ofleads 5 are positioned in close proximity to the stimulating electrode,about 2 cm. from the pacing or first set of leads 4 in the direction ofthe antrum 12. Of course the functions of stimulating and sensing may beequally performed by both sets of leads, i.e. each set of leads may beused to both sense and stimulate the tissues.

FIG. 2 details the preferred positioning of an electrode of a leadwithin the various layers of the stomach. As seen, the stomach 10 hasessentially seven layers of tissue. In the preferred embodiment, theelectrode of each lead is positioned into the layers of the stomachmuscle as shown. That is, the electrode is positioned such that itintersects both the longitudinal and circular layers. This is believedimportant by the inventor because in such a manner the electrode is ableto also intersect the integral nerve fibers of the stomach, carried withthe cells of Cajal. Of course, other types of electrodes or lead systemsmay be used, including those which contact only any one of each of thelayers of the stomach organ, such as only the mucosa or only the serosa.Moreover, although in the preferred embodiment a pair of unipolar leadsare used for stimulation and a second pair of unipolar leads are usedfor stimulation, other configurations of leads may be used, such asbipolar, tripolar, quadrapolar, as well as any other suitableconfiguration.

FIG. 3 depicts a plan view of the preferred embodiment lead 15 used inthe present invention. As seen, the lead 15 essentially has threesections, connector section 16, body section 17 and fixation section 18.Connector section 16 includes a connector pin 22 to electrically couplethe lead 15 into the pulse generator. Any connector pin 22 as well knownin the art may be used. Body section 17 includes an electrical conductor19 surrounded by an electrical insulator 20. In the preferred embodimentelectrical conductor 19 is a platinum iridium alloy and electricalinsulator 18 is silicone. Of course, other biocompatible materials mayalso be used.. As seen, at the distal end of the body section 17 is anelectrode 25. In the preferred embodiment, electrode 25 is a polishedplatinum iridium alloy. Of course, other materials may likewise be used,such as a porous platinized structure. In addition, the electrode 25could further feature various pharmaceutical agents, such asdexamethasone sodium phosphate or beclomethasone phosphate in order tominimize the inflammatory response of the tissue to the implanted lead15. Located distal to the electrode 25 is the fixation section 18. Asseen, fixation section 18 has essentially two piece parts, a suture 26which is in turn coupled to a needle 27. Suture 26 includes a fixationcoil 28 along its length. Needle 27 is preferably curved. As is wellknown in the art, fixation coil 28 cooperates with the body tissue afterimplantation to maintain the lead 15 in the position implanted. Ofcourse, other fixation mechanisms may be used, such as fixation discs,as is well known in the art.

FIG. 4 depicts a functional block diagram of the gastrointestinal pulsegenerator according to the present invention. As seen, pulse generator 3is enclosed by hermetic enclosure 40 to protect pulse generator 3 whenimplanted. Hermetic enclosure may consist of any suitable construction.Pulse generator 3 couples with two sets of leads 4, 5 which are, inturn, coupled to the stomach 10. The first set of leads 4 transmitsstimulation pulses from pulse generator 3 to the stomach. The second setof leads 5 provide sensing of the gastro electrical activity of thestomach 10 to the pulse generator 3. Although in the preferredembodiment the stimulating leads and sensing leads are separate leads,the present invention may also be employed using a combination of leadwhich both sense and stimulate.

As seen, the sensing leads 4 are coupled into a slow wave detectioncircuit 41. Slow wave detection circuit 41 includes a band passamplifier, a slew rate converter and two threshold detectors.Essentially, such a slow wave detection circuit 41 is similar to thoseused in a cardiac pacemaker but with several important characteristics.First, the band pass amplifier has a much lower center frequency,preferably on the order of 0.3 Hz (18 bpm). The slew rate convertergenerates a signal corresponding to the sensed slew rate of the sensedsignal. The output of the slew rate detector, as is well known in theart, is directly related to the sensed slew rate of the sensed signal.The threshold detectors generate output signals when the sensed inputsignal is above a threshold level. One threshold detector correspondsthrough the band pass amplifier to the peak to peak amplitude of thesensed electrogastrogram. The second threshold detector corresponds tothe sensed slew rate.

Preferably, the slow wave detection circuit 41 must be able to detectinput signals between 30 microvolts and 10 millivolts which have a slewrate between 100 microvolts per/second up to 10 millivolts per/secondwith a typical value of 1 millivolt per second. Such a range may beachieved using multiple steps which are controlled by the microprocessor46 via the input line 46b-41d. To detect the slow wave, both thresholddetectors should be coupled using a logical OR configuration. Thus, asignal should then be sent via the output line 41c-46a to themicroprocessor 46. The slew rate detector may also include aninterference detector specially designed to detect power fieldvariations as is well known in the pacing art.

The band pass amplifier should be blanked for a period after a sensedevent has been received by the microprocessor 46 or just beforestimulation pulse is emitted by output stage discussed below. Themicroprocessor 46 should also ignore sensed output signals during aperiod after a sensed or paced event. This is similar to a blankingcircuit where sensed events during a blanking period do not affect thetiming of the pulse generator. In the preferred embodiment, the blankingperiod is on the order of between 0.5 to 3.0 seconds. After the blankingperiod, during a certain timing window, the microprocessor 46 mayreceive slow wave detection signals, which will not restart the pulsegenerator timing circuit, but will instead be interpreted asinterference by the microprocessor 46. This timing window, interferencedetection timing window, may be up to seven seconds in duration afterthe sensed or paced event.

As seen, blanking switch 42 is coupled to sensing electrodes 4 as wellas to amplifier 45. The operation of blanking switch 42 causes theamplifier 45 to be connected to the sensing electrodes 4 once anintrinsic deflection has been detected or a stimulus has been emitted.Preferably, this occurs after a short delay. Blanking switch 42 isclosed between 1 to 2 seconds after the events and opens roughly 5 to 7seconds later or at approximately 30% of the intrinsic event interval.As seen, the switch is controlled via the line 6e-2e.

Also coupled to the sensing electrodes 4 is an AC current generator 43.This AC current generator 43 is part of a plethysmorgraphy circuit.Overall, the plethysmorgraphy circuit is comprised from AC currentgenerator 43, amplifier, modulator and ADC converter 44 as well as aportion of the microprocessor 46. The AC current generator 43 isswitched on via signal from microprocessor 46 once a slow wave isdetected or a pacing stimulus is emitted. It is switched off roughly 10seconds after being switched on also from the same line or signal fromthe microprocessor 46. The AC current generator 43 amplitude andfrequency are programmable via microprocessor 46. The frequency shouldbe such it is not detected by amplifier 4. If synchronous detection byamplifier 4 occurs at the end of the blanking period, then the amplitudeand/or the frequency of approximately the AC current generator 43 isadjusted by the microprocessor 46 to avoid subsequent detection of thegenerated AC current. Overall, the plethysmorgraphy circuit is presentto provide a means for sensing mechanical activity of the underlyingtissue. That is, whereas the electrogastrogram may be sensed usingelectrical pickups, the contraction of the gastrointestinal tract may besensed using the plethysmorgraphy circuit.

Turning now to the amplifier, the modulator and ADC converter 44, the ACvoltage caused by the injection of AC current generator 43 is amplifiedand demodulated and converted in order to detect impedance changescaused by contractions of the underlying tissue. The ADC converterdigitizes the amplitude of the demodulated signal. The digitized signalis transmitted via line 44c-46h to the microprocessor 46. Themicroprocessor 46 analyzes the signal pattern by comparing it with oneor more templates to identify it as a contraction as well as to rejectinterference or signals generated by postural changes or vomiting. Thistemplate comparison is done synchronously with the detection of the slowwave. Line 46i-44d is used to control the amplifier and ADC from themicroprocessor 46.

The microprocessor 46 handles all timings and data storage of the pulsegenerator and may be of any suitable design. The description of themicroprocessor 46 function is described in the section below whichdetails the operation of the algorithm used in the present invention.

Stimulation pulses are generated by the output stage 47. In thepreferred embodiment, the output stage 47 generates pulse trainsconsisting of 2 pulses of 300 microseconds duration each spaced apart byone second, where each pulse train, in turn is further spaced apart by 4seconds. Of course, many other pulse trains may also be delivered,including constant current or constant voltage outputs, or a mixture ofboth. The output pulses are transported to the gastrointestinal tissuevia medical electrical leads 5 and thus to the stomach.

Turning again to the output stage 47, when an output pulse is to bedelivered, its amplitude, pulse width and duration and frequencies arecontrolled via lines 46j-47a. If it is a burst of stimuli, the frequencyand duration are controlled through the same line while a burst finishedsignal is sent to the microprocessor 46 via output line 47b-46k.

Programmability to the pulse generator 3 is achieved throughreceiver-demodulator 48 and transmitter 49. As seen, each of thesedevices is coupled to the microprocessor 46. The receiver-demodulator 48and transmitter 49 are similar to those used in cardiac pacemakers.

FIG. 5 is a table listing the gastric arrhythmias or abnormalities whichmay be detected and treated using the present invention. In thepreferred embodiment, the gastric arrhythmias or abnormalities areprocessed or detected using either a zero-crossing analysis orcross-correlation or both. As seen, in the present invention, thedetection of an arrhythmia is used with a zero-crossing analysis. Thedecision making threshold is the period between gastric slow waves isgreater than approximately 30 seconds. Of course, other values may beused. Bradygastria is defined on a similar basis as an arrhythmia. If astable period greater than approximately 30 seconds is sensed, then abradygastria is detected. Dysrhythmia is detected if irregular periodsof the EGG exhibits cyclic activities having variations of more than 10%in the period of successive cycles of the activity. As seen, this isdetermined using the simple mathematical formula of averaging theperiods between two sensed slow waves and whether or not the periodvariation is greater than 0.1 which corresponds to 10%. Mathematically,this is expressed as |(T_(i) -T_(i+1))/T_(i) |>0.1 Tachygastria isdetected also using zero-crossing analysis and is detected if a stablesignal of the successive period of less than 16 seconds is detected. Twoother types of abnormalities are also detected using the presentinvention using a zero-crossing analysis. As seen, the retrogradepropagation is detected by examining the relative phase angle betweentwo signals. If the more distal signal sensed is in advance of or leadsthe proximal signal sensed, then retrograde propagation is detected.Uncoupling is also detected using cross-correlation techniques. As seen,uncoupling is detected by comparing the two channels, and if theyexhibit dissimilar periods between the two slow waves then uncoupling isdetected.

Turning now to FIG. 6 which illustrates the detection interval rangeswhich may be employed in a preferred embodiment of the presentinvention. The specific interval ranges are selected and programmable bythe physician. As seen, events which occur less than one second apartare not detected due to blanking. This is a fixed interval and itslength is not programmable by the physician. The range of intervalsbetween detected events taken as indicative of tachygastria are greaterthan 1 second and less than 16 seconds. That is, the tachygastriadetection interval extends to 16 seconds. This range is programmed andis selected by the physician to suit the particular patient and the leadconfiguration. used. The lead of intervals between detected events takenas indicative of normal gastric rhythm are greater than approximately 16seconds and less than approximately 30 seconds. That is, the normalgastric rhythm detection interval extends to approximately 30 seconds.This range is also programmed and is selected by the physician to suitthe particular patient and leads used. Events having intervals whichoccur after approximately 30 seconds up to approximately 60 seconds, inthe preferred embodiment, are taken as indicative of bradygastria. Thatis, the bradygastria escape interval extends up to approximately 60seconds. This range is also programmed and is selected by the physician.Events which occur at intervals greater than the bradygastria escapeinterval would not be detected as the bradygastria escape interval wouldtime out at 60 seconds and the device would recycle and deliver atherapy. Examples of how these detection intervals function are asfollows. If a first event is sensed and a second event is sensed 10seconds later, then a tachygastria is provisionally detected. If a firstevent is sensed and a second event is sensed 40 seconds later, then abradygastria is provisionally detected. As a third example, if a firstevent is sensed and a second event occurs less than one second later anda third event occurs 20 seconds after the first event, then a normalgastric rhythm is sensed. This is so because the second event occurredduring the blanking period and thus was not sensed (the third event wasthereafter sensed a sum of 20 seconds after the first event, well withinthe normal gastric rhythm interval range).

It should be noted that these specific times for the intervals is forthe preferred embodiment and thus is only illustrative of the presentinvention. Other interval ranges may also be used within the scope ofthe present invention.

FIG. 7 is a functional block diagram illustrating the present invention.As seen, the present invention senses as, a first step, theelectrogastrogram. This is accomplished using the sensing leads boarddepicted in FIG. 1. Next, the electrogastrogram is digitized using themicroprocessor. Next, the amplitude, period and slew rate of theelectrogastrogram are analyzed. If either the amplitude or period orslew rate of the electrogastrogram are abnormal, then the device dropsdown to identify the gastroarrhythmia detected. Such identification ofthe gastroarrhythmia is done using the criteria set forth in FIG. 5,discussed above. Once an accurate diagnosis has been reached using thecriteria set forth in FIG. 5, then the device proceeds to emitelectrical stimulation pulse trains for a preset period of time. If,however, the amplitude and period and slew rate of the electrogastrogramare normal, then the device resets itself and proceeds back to sense theelectrogastrogram.

FIG. 8 details the preferred stimulation pulse train emitted. As seen,the preferred pulse train consists of two pulses P-1 and P-2 of 300microseconds duration each spaced apart by 1 second, where each pulsetrain, in turn, is further spaced apart from one another by 4 seconds,as illustrated. Of course, many other pulse trains and timing schemesmay also be delivered, including constant current or constant voltageoutputs, or a mixture of both. The output pulses are transported to thegastrointestinal tissue via medical electrical leads 5 and thus tostomach.

FIG. 9 details an alternative embodiment of pulse trains delivered for apreset period of time to the stomach. As seen, in this alternativeembodiment, pulse trains P-1 and P-2 are delivered which have adecreasing amplitude.

FIG. 10 and FIG. 11 further detail alternative embodiments for pulsetrains used to stimulate the stomach for a preset period of time. Asseen in FIG. 10 a pulse train having pulses P-1, P-2 and P-3 ofincreasing amplitude is delivered. In FIG. 11 a biphasic pulse train ofpulses P-1 and P-2 is delivered.

FIG. 12 depicts an exemplary EGG as detected by the present inventionand the emitted stimulation to treat a detected arrhythmia. As seen, theEGG typically exhibits periodic slow waves of approximately 25 secondsapart. As seen, slow wave 12-1 is followed by 12-2. Following the slowwave 12-2, another slow wave does not occur. As seen, the detectionintervals are retriggered after each detected slow wave. In the example,the detection intervals which begin timing after slow wave 12-2 time outthrough the Tachygastria escape interval (TGEI) through the normalgastric rhythm escape interval (NGREI) and complete timing out throughthe end of the bradygastria escape interval (BGEI)I. Once thebradygastria escape interval (BGEI) is reached, the stimulation channelis activated in a series of pulse trains 12-4, 12-5 and 12-6 areinitiated. These pulse trains are emitted for preset periods of time, inthe examples shown for a period of 90 seconds. Once the preset period oftime times out, the device again recycles to sense the EGG and detectwhether or not a gastroarrhythmia is present. As seen, because slow wave12-7 is sensed within the normal escape interval, no further electricalstimulation pulse trains are emitted.

Turning now to FIG. 13, this depicts a gastroarrhythmia which isdetected due to the fact that the slew rate of the electrogastrogram isnot normal. As seen, slow wave 13-1 is followed by slow wave 13-2. Slowwave 13-2, however, has an additional slew rate or slope of incomingexcursion signal 13-3 less abrupt than that shown in 13-1. Due to thisfact, the device then drops down and identifies the gastroarrhythmia. Inresponse to the identified gastroarrhythmia, the device emits electricalstimulation pulse trains 13-4, 13-5 and 13-6 for a preset period of timeto treat the detected arrhythmia.

FIG. 14 depicts a further gastroarrhythmia detected. As seen, slow waves14-1, 14-2 are followed by a slow wave 14-3, having a much loweramplitude. As seen, in response to this sensed lower amplitude, thedevice emits electrical stimulation pulse trains for a preset period oftime 14-4, 14-5, and 14-6.

FIG. 15 depicts an example of a gastroarrhythmia which is detected bythe present invention using cross-correlation. As seen, slow wavestypically begin in the pacemaker area located in the proximal gastricbody along the greater curve as shown by the gray area. As discussedabove, these slow waves spread circumferentially and distally andmigrate through the antrum. These slow waves would be sensed by sensingelectrodes C and D. The slow wave amplitude is higher and thepropagation loss is faster in the distal antrum compared with thecorpus. As seen, the slow wave dissolves in the terminal antrum whileanother slow wave begins to migrate distally again from the pacemakerregion. Thus, as shown, three slow waves will propagate from proximal todistal stomach every 60 seconds. On occasion, the slow waves may becomeuncoupled or out of phase with one another. This is taken as anindicative of a gastroarrhythmia and would elicit an electricalstimulation for a preset period of time by the present invention. Inthis particular example, these slow waves have a greater period betweenone another than those otherwise normally seen. The effect of thisuncoupling is that the slow waves depict retrograde propagation. That isthe proximal sites are coupled to but lag in time relative to the distalsites. This is an abnormality detectable using a cross correlationtechnique, typically programmed into the microprocessor.

FIG. 16 depicts an example of a gastro rhythm which is detected by thepresent invention using separate frequency sensors. In particular FIG.16 depicts the stomach undergoing a peristaltic contraction and thecorresponding electrogastrogram along the same portions of the stomach.As seen, the peristaltic wave moves through the stomach towards thepyloric antrum. The peristaltic contraction functions to both forcecontents of the stomach into the duodenum as well as to create shear onthe stomach contents and thus break the contents down into smallerparticles. During a peristaltic contraction, the stomach continues toundergo slow waves 16-1. As seen, these slow waves typically occur at arate of approximately 3 per minute. During a peristaltic contraction,however, the slow waves further feature a high frequency actionpotential. As seen, each slow wave features a corresponding highfrequency action potential 16-2 shortly thereafter. The slow waves, asdiscussed above, typically have a frequency of approximately 3 perminute. The higher frequency action potentials, however, typically havea frequency of between approximately 100-300 hertz. Thus a furtherembodiment of the present invention is directed to sensing both the slowwaves and the higher frequency fast waves which follow and processingthe sensed waves to indicate the state of the stomach at that moment.This is especially useful to thereby determine or detect the presence orabsence of peristaltic contraction within the stomach or any othersmooth muscle organ of the body.

FIG. 17 depicts the steps used to sense the rhythm shown in FIG. 16. Asseen, at the first step 901, the electrogastrogram is sensed. Next, at902 the electrogastrogram is digitized using the microprocessor. Next,the digitized data is analyzed for both a low frequency wave 903 andwhether an higher frequency wave follows 904. If both a low frequencywave is detected which is followed by a high frequency wave 905, thenthe device drops down to signal peristalsis is occurring 906. If,however, only a low frequency wave or only a high frequency wave isdetected, then the device resets itself and proceeds back to sense theelectrogastrogram at step 901.

FIG. 18 shows a block diagram of an alternate embodiment of the presentinvention. That is in this alternate embodiment, the present inventionmay be practiced completely in the context of a software based system.As seen In this embodiment system 118 includes an implantable stimulator120 which is used in conduction with an external programmer 146.Stimulator 120 includes an output connector 121 through which one ormore medical electrical leads 124 may be connected to internal circuitsof stimulator. In this embodiment lead is also typically Medtronic model4300 intramuscular lead. Although a single lead 124 is shown used tocouple stimulator 20 to gastrointestinal tract, it is to be understooduse of a single lead in this manner is only exemplary, as the inventionmay be used equally well with systems that include multiple leads thatmake contact with multiple locations within gastrointestinal tract orother body tissue locations.

Included within internal circuits of stimulator with which lead 124makes contact when inserted into connector 121 include an outputamplifier 134 and a sense amplifier 136. Output amplifier 134 generatesan electrical stimulation pulses 135 as controlled by a pulse generator132. Pulse generator 132, in turn, receives timing signals from acontrol processor 130. Such timing signals control when stimulationpulses 135 are to be generated. Sense amplifier 136 monitors electricalsignals appearing on lead 124, and processes such signals.

Processing typically includes amplification, filtering, and thresholddetection. If a valid depolarization signal ("intrinsic event") issensed by sense amplifier 136, then sense amplifier provides anappropriate signal to control processor 130 of such sensed intrinsicevent. If no valid intrinsic events are sensed during a prescribed timeperiod, referred to generally as "escape interval," then controlprocessor 130 signals pulse generator to generate a stimulation pulse.If a valid intrinsic event is sensed before escape interval times out,control processor responds by resetting escape interval, therebypreventing pulse generator from generating a stimulation pulse. In thismanner, stimulator provides stimulation pulses only when needed, e.g.,Only when a valid intrinsic event is not sensed.

Control processor 130, which may be a microprocessor or equivalentprocessing circuit, operates in accordance with a control program thatis stored in stimulator memory 140. Also stored in memory is a set ofcontrol parameters that are used by control program as it definesoperation of processor. That is, control parameters define variousvariables associated with operation of stimulator, such as duration ofescape interval, frequency, interpulse interval, duration, amplitude andrelative timing parameter for each of stimulation pulses and like. Clockcircuit 138 provides necessary clock signals for operation of controlprocessor 130. Control program specifies particular order or sequence ofevents that are carried out by processor. For example, control programmay specify that, upon detecting a valid intrinsic event, a controlparameter stored in a particular address in memory should be retrievedin order to define an appropriate corresponding delay. Control programmay further specify that if a further valid intrinsic event is sensedbefore delay times out, then another control parameter stored in anotherlocation (address) of memory 40 should be retrieved in order to definean appropriate delay. If a valid intrinsic event is not sensed beforetiming out of delay, then control program may specify another memoryaddress where a control parameter is stored that defines amplitude andpulse width of a stimulation pulse train that is to be generated.

Of course, above example is extremely simple, but it illustrates basicoperation of stimulator. Those skilled in art will recognize that thereare numerous events associated with gastrointestinal cycle, and that reare numerous types of cycles that may occur. Control program, incombination with other control circuitry within stimulator, thus definehow stimulator responds to each possible event and intrinsic cycle type.Control parameters, in turn, define magnitude of variables associatedwith such response, e.g., Duration of time periods, amplitude and widthsof stimulation pulses, gain of amplifiers, threshold level of thresholddetectors, and like.

In order to add flexibility to operation of stimulator 20, stimulatoralso includes a telemetry circuit 142. Telemetry circuit 142 allowsaccess to memory 140 from a remote location, e.g., From an externalprogrammer 146 at a non-implanted location. External programmer 146includes means for establishing a telemetry link 144 with telemetrycircuit 142 of implanted stimulator. Through this telemetry link 144,control parameters may be sent to telemetry circuit 142 for storage inmemory 140. Such control parameters may thereafter be used by controlprogram stored in memory 140 to steer operation of stimulator 120, asexplained above. Additional details associated with design and operationof a telemetry circuit 142, as well as an external programmer 146, maybe found in U.S. Pat. Nos. 4,809,697 and 4,944,299, incorporated hereinby reference.

External programmer 146 is used to programmably set control parametersassociated with operation of control processor 130. In contrast tocontrol program, which preferably is fixed, certain control parametersthat define variables used by control program (or equivalent circuitry)in controlling stimulator may be readily changed, from time to time,after implantation by using external programmer 146. Thus, should therebe a need to change a given control parameter, e.g., Stimulation pulseamplitude generated by output amplifier 134, sensitivity (thresholdsetting) of sense amplifier 136, or other variables, then appropriatecontrol parameters that define such variables are simply updated(programmed) through telemetry link established by external programmer146. Such programming of control parameters is limited, however, so thatassociated variables can only be changed within certain safe limits thatare defined by control program and/or o circuitry within stimulator.

Memory is preferably a RAM-type memory which has both a control programand a set of control parameters stored rein at respective memorylocations (addresses). Like conventional programmable stimulators, setof control parameters in memory 140 may be selectively updated(programmed), as needed, through use of external programmer 146. Controlprogram stored in memory 40 may also be updated, using appropriatesafeguards, through use of external programmer 146. Thus, when newfeatures requiring a new control program are added to stimulator, apatient having an existing implanted stimulator can receive benefits ofsuch new features by simply upgrading control program stored in his orher implanted stimulator. In this manner, system permits an existingcontrol program stored in an implanted stimulator to be non-invasivelyupgraded to a new version of control program.

Although the invention has been described in detail with particularreference to a preferred embodiment and alternate embodiments thereof,it will be understood variations and modifications can be effectedwithin the scope of the following claims. Such modifications may includesubstituting elements or components which perform substantially the samefunction in substantially the same way to achieve substantially the sameresult for those described herein.

What is claimed is:
 1. An apparatus for providing stimulation to thegastrointestinal tract comprising:a housing, means for sensingelectrical activity of the gastrointestinal tract between the frequencyof approximately 1 to 15 cycles/min. positioned within the housing, acontroller positioned within the housing, the controller coupled to themeans for sensing, means for generating electrical stimulation pulsetrains, the means for generating electrical stimulation pulse trainscontrolled by the controller and positioned within the housing; andmeans for electrically coupling the means for generating to agastrointestinal tract of a patient.
 2. The apparatus of claim 1 whereinthe signal processor comprises a bandpass amplifier responsively coupledto the means for sensing the bandpass amplifier producing a bandpassfiltered signal from the sensed signal, anda zero-level detector coupledto the bandpass amplifier to thereby produce a pulse train of afrequency component proportional to a highest amplitude spectralcomponent of the bandpass signal.
 3. The apparatus of claim 1 furthercomprising means for recording the intrinsic gastrointestinal electricalactivity for a preset period of time in response to the sensing of anabnormal electrical activity signal.
 4. An apparatus for providingstimulation to the gastrointestinal tract comprising:a medicalelectrical lead having means for coupling to the gastrointestinal tractof a patient; a sensor for sensing intrinsic gastrointestinal electricalactivity between the frequency of approximately 1 to 15 cycles/min.; asignal processor to process the sensed intrinsic gastrointestinalelectrical activity between the frequency of approximately 1 to 15cycles/min. (0.017-0.25 Hz) and generate an abnormal gastrointestinalelectrical activity trigger signal when abnormal gastrointestinalelectrical activity is sensed; a pulse generator, the pulse generatorcoupled to the signal processor so as to receive the abnormalgastrointestinal electrical activity trigger signal, the pulse generatorcoupled to the medical electrical lead, the pulse generator emittingstimulation pulse trains for a pre-set period of time in response to theabnormal gastrointestinal electrical activity trigger signal from thesignal processor.
 5. The apparatus of claim 4 wherein the signalprocessor comprises a bandpass amplifier responsively coupled to themeans for sensing the bandpass amplifier producing a bandpass filteredsignal from the sensed signal; anda zero-level detector coupled to thebandpass amplifier to thereby produce a pulse train of a frequencycomponent proportional to a highest amplitude spectral component of thebandpass signal.
 6. The apparatus of claim 4 further comprising meansfor recording the intrinsic gastrointestinal electrical activity for apreset period of time in response to the generation of an abnormal;electrical activity signal.
 7. An apparatus for providing stimulation tothe gastrointestinal tract comprising:a medical electrical lead havingmeans for coupling to the gastrointestinal tract of a patient; a sensorfor sensing intrinsic gastrointestinal electrical activity between thefrequency of approximately 1 to 15 cycles/min.; a signal processor toprocess the sensed intrinsic gastrointestinal electrical activitybetween the frequency of approximately 1 to 15 cycles/min. and generatean abnormal gastrointestinal electrical activity trigger signal whenabnormal gastrointestinal electrical activity is sensed; a pulsegenerator, the pulse generator coupled to the signal processor so as toreceive the abnormal gastrointestinal electrical activity triggersignal, the pulse generator coupled to the medical electrical lead, thepulse generator emitting stimulation pulse trains only during the timethe abnormal gastrointestinal electrical activity trigger signal isreceived.
 8. The apparatus of claim 7 wherein the signal processorcomprises a bandpass amplifier responsively coupled to the means forsensing the bandpass amplifier producing a bandpass filtered signal fromthe sensed signal;a zero-level detector coupled to the bandpassamplifier to thereby produce a pulse train of a frequency componentproportional to a highest amplitude spectral component of the bandpasssignal.
 9. The apparatus of claim 8 further comprising means forrecording the intrinsic gastrointestinal electrical activity for apreset period of time in response to the generation of an abnormalelectrical activity signal.
 10. An apparatus for providing on-demandstimulation of the gastrointestinal tract comprising:a housing, thehousing having means for detecting cyclic activity of smooth muscle;means for processing the detected cyclic activity of smooth musclegreater than approximately 5 cycles per minute or less thanapproximately 2 cycle per minute, the means for processing emitting anabnormal gastrointestinal activity signal when the cyclic activity ofsmooth muscle is greater than approximately 5 cycles per minute or lessthan approximately 2 cycle per minute is processed; means for detectingthe emission of the abnormal gastrointestinal activity signal by theprocessing means and generating electrical stimulation in response tothe abnormal gastrointestinal activity signal; means for electricallycoupling the means for generating to a gastrointestinal tract of apatient.
 11. The apparatus of claim 10 wherein the means for processingemitting an abnormal gastrointestinal activity signal when the cyclicactivity of smooth muscle greater than approximately 5 cycles per minuteor less than approximately 2 cycle per minute is processed; and meansfor emitting electrical stimulation in response to the abnormalgastrointestinal activity signal.
 12. The apparatus of claim 10 whereinthe means for processing the detected cyclic activity of smooth muscleprocesses the detected cyclic activity of smooth muscle which is greaterthan approximately 10 cycles per minute or less than approximately 1cycle per minute.